Cathepsin B activity is required for NALP3-induced caspase-1 activation, lysosomal dysfunction and cell death in macrophages. (135.81)
Bibliographic record
Abstract
Abstract The nucleotide-binding and leucine-rich repeats (NLRs) are a family of innate immune receptors sensing various pathogen- and danger-associated molecules within the cytosol. Activation of NLRs such as NALP3 induces the secretion of inflammatory cytokines such as interleukin (IL)-1ß and rapid cell death, through caspase-1 activation. To date, the mechanisms associated with NALP3 activation and cell death remain poorly defined. This study examined whether lysosomal membrane dysfunction or the lysosomal protease, cathepsin B (CTSB), are involved in cell death induced by NALP3. Wild-type (WT), NALP3-, ASC-, caspase-1- and CTSB-deficient immortalized bone marrow-derived macrophages were exposed to the NALP3 activator ATP. ATP treatment caused lysosomal dysfunction measured by loss of acridine orange, caspase-1 activation and rapid cell death in WT but not in NALP3-, ASC-, caspase-1- or CTSB-deficient macrophages. Mutant Pseudomonas aeruginosa (exotoxin U deficient) induces IPAF-dependent IL-1ß release and cell death. The mutant bacteria induced cell death and IL-1ß release in WT and CTSB-deficient macrophages but not in IPAF-, ASC- or caspase-1-deficient macrophages. Altogether, these results suggest that cathepsin B is required for NALP3-induced but not IPAF-induced caspase-1 activation and lysosomal dysfunction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".